A Study to Assess Cardiovascular Outcomes Following Treatment With Omarigliptin (MK-3102) in Participants With Type 2 Diabetes Mellitus (MK-3102-018)

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ClinicalTrials.gov Identifier: NCT01703208

Recruitment Status :
Terminated
(The study was terminated for business reasons and not due to any safety or efficacy concerns related to omarigliptin)

Number of Participants With an Event Per 100 Person-Years for First Event of MACE (Confirmed CV-Related Death, Fatal and Nonfatal MI, and Fatal and Nonfatal Stroke) [ Time Frame: Up to 179 weeks ]

Participants with an event of MACE (confirmed cardiovascular, CV-related death, fatal and nonfatal myocardial infarction [MI], and fatal and nonfatal stroke). Person-years were calculated as the sum of all participants' follow-up time to first event.

A1C is blood marker used to report average blood glucose levels over prolonged periods of time and is reported as a percentage (%). This change from baseline reflects the Week 18 A1C minus the Week 0 A1C.

Change From Baseline in A1C at Week 18 in a Sub-Study of Participants Taking Insulin (With or Without Metformin) [ Time Frame: Baseline and Week 18 ]

A1C is blood marker used to report average blood glucose levels over prolonged periods of time and is reported as a percentage (%). This change from baseline reflects the Week 18 A1C minus the Week 0 A1C.

Percentage of Participants Who Experienced at Least One Adverse Event in a Sub-study of Participants Taking Insulin Excluding Data After Background Antihyperglycemic Agent (AHA) Change [ Time Frame: Up to Week 18 ]

An AE is defined as any unfavorable and unintended sign including an abnormal laboratory finding, symptom or disease associated with the use of a medical treatment or procedure, regardless of whether it is considered related to the medical treatment or procedure, that occurs during the course of the study.

Percentage of Participants Who Discontinued From Study Drug Due to an Adverse Event in a Sub-Study of Participants Taking Insulin Excluding Data After Background AHA Change [ Time Frame: Up to Week 18 ]

An AE is defined as any unfavorable and unintended sign including an abnormal laboratory finding, symptom or disease associated with the use of a medical treatment or procedure, regardless of whether it is considered related to the medical treatment or procedure, that occurs during the course of the study.

Number of Participants With an Event of CV-Related Death [ Time Frame: Up to 179 weeks ]

Participants with adjudicated and confirmed AEs of cardiovascular-related death.

Number of Participants With an Event Per 100 Person-Years of CV-Related Death [ Time Frame: Up to 179 weeks ]

Participants with adjudicated and confirmed AEs of cardiovascular-related death. Person-years were calculated as the sum of all participants' follow-up time to event.

Number of Participants With an Event of First MI (Fatal and Non-fatal) [ Time Frame: Up to 179 weeks ]

Participants with adjudicated and confirmed AEs of fatal and non-fatal MI.

Number of Participants With an Event Per 100 Person-Years of First MI (Fatal and Non-fatal) [ Time Frame: Up to 179 weeks ]

Participants with adjudicated and confirmed AEs of fatal and non-fatal MI. Person-years were calculated as the sum of all participants' follow-up time to first event.

Number of Participants With an Event of Stroke (Fatal and Non-fatal) [ Time Frame: Up to 179 weeks ]

Participants with adjudicated and confirmed AEs fatal and non-fatal stroke.

Number of Participants With an Event Per 100 Person-Years of First Stroke (Fatal and Non-fatal) [ Time Frame: Up to 179 weeks ]

Participants with adjudicated and confirmed AEs fatal and non-fatal stroke. Person-years were calculated as the sum of all participants' follow-up time to event.

Number of Participants With an Event of All-Cause Death [ Time Frame: Up to 179 weeks ]

All-cause death was death from any cause.

Number of Participants With an Event Per 100 Person-Years of the Event of All-Cause Death [ Time Frame: Up to 179 weeks ]

All-cause death was death for any cause. Person-years were calculated as the sum of all participants' follow-up time to event.

Change From Baseline in A1C at Week 142 [ Time Frame: Baseline and Week 142 ]

A1C is blood marker used to report average blood glucose levels over prolonged periods of time and is reported as a percentage (%). This change from baseline reflects the Week 142 A1C minus the Week 0 A1C.

Time to Initiation of Long-Term Insulin Therapy in Participants Not Receiving Insulin at Baseline [ Time Frame: Up to 179 weeks ]

Long-term insulin therapy was defined as a continuous period of insulin use of more than 3 months.

Percentage of Participants Who Experienced at Least One Adverse Event [ Time Frame: Up to 234 weeks ]

An AE is defined as any unfavorable and unintended sign including an abnormal laboratory finding, symptom or disease associated with the use of a medical treatment or procedure, regardless of whether it is considered related to the medical treatment or procedure, that occurs during the course of the study.

Percentage of Participants Who Discontinued From Study Drug Due to an Adverse Event [ Time Frame: Up to 212 weeks ]

An AE is defined as any unfavorable and unintended sign including an abnormal laboratory finding, symptom or disease associated with the use of a medical treatment or procedure, regardless of whether it is considered related to the medical treatment or procedure, that occurs during the course of the study.

Change From Baseline in FPG at Week 18 in a Sub-Study of Participants Taking Insulin [ Time Frame: Baseline and Week 18 ]

The purpose of this study is to evaluate the cardiovascular (CV) safety profile of omarigliptin in participants with type 2 diabetes mellitus (T2DM). The primary hypothesis is that treatment with omarigliptin 25 mg once weekly is non-inferior to treatment with placebo and active comparators across the omarigliptin program with regard to the risk of developing a confirmed event in the primary CV composite endpoint.

Detailed Description

The trial was amended to extend the length of the trial in order to meet FDA requirements for the post-approval assessment of cardiovascular (CV) safety. The trial now contains 2 time intervals: Period 1 and Period 2. Period 1 refers to the time interval up to this recent protocol amendment and Period 2, the time interval from this protocol amendment until the end of the study. Participants in Period 1 will be re-consented and continue into Period 2. If required, additional participants will be enrolled in Period 2. Stage 1 refers to the prefiling United States Food and Drug Administration (US FDA) requirement to rule out a 80% increased CV risk. Stage 2 refers to the US FDA post-marketing requirement to rule out a 30% increased CV risk. The Stage 1 assessment of CV risk occurred during Period 1 and was based on a meta-analysis of major adverse CV events (MACE) and unstable angina across the omarigliptin Phase 2/Phase 3 program. The Stage 2 assessment will be based on MACE in P018 alone including CV events from both Period 1 and Period 2.

* Includes publications given by the data provider as well as publications
identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.

Recruitment Information

Recruitment Status ICMJE

Terminated

Actual Enrollment ICMJE (submitted: August 17, 2015)

4202

Original Estimated Enrollment ICMJE (submitted: October 5, 2012)

4000

Actual Study Completion Date

March 22, 2017

Actual Primary Completion Date

May 13, 2016 (Final data collection date for primary outcome measure)

Eligibility Criteria ICMJE

Inclusion Criteria:

Diagnosed with type 2 diabetes mellitus

Is on one of the following diabetes treatment regimens that is stable for at least 12 weeks (except for pioglitazone for at least 16 weeks) and is within the associated A1C range for that treatment regimen:

A1C >= 7.0% and <=10.0% (>=53 mmol/mol and <=86 mmol/mol) on (a) monotherapy with a sulfonylurea or meglitinide OR (b) dual combination therapy with a sulfonylurea or a meglitinide and MF, PIO, AGI, or SGLT2i OR

(1) Male; (2) female not of reproductive potential; or (3) female of reproductive potential who agrees to remain abstinent or use alone or in conjunction with their partner 2 methods of contraception to prevent pregnancy during the study and for 21 days after the last dose of study drug.

On a weight loss program and is not in the maintenance phase or has been on a weight loss medication in the past 6 months or has undergone bariatric surgery within 12 months prior to study participation